Shyamala Navada, M.D., and colleagues from the Mount Sinai School of
Medicine presented a poster entitled “Evaluation of Rigosertib in
Patients with a Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia
(AML) Relapsed or Refractory to Hypomethylating Agents: A Phase I/II
Study.” Dose and duration of exposure of single agent rigosertib were
evaluated in this study. Investigators found that single agent
rigosertib was well tolerated and achieved effects that were in line
with previously published clinical studies of the drug in MDS and AML,
supporting continued development of rigosertib.

Lakshmikanth Katragadda, M.D., and colleagues from the MD Anderson
Cancer Center presented a poster entitled “Phase1/2 Single Arm Study of
Rigosertib (ON 01910.Na) In Patients (Pts) with Relapsed or Refractory
Acute Leukemia or Transformed Myeloproliferative Neoplasms.” In this
study, patients received a fixed dose of rigosertib (2400 mg/day) by
continuous intravenous infusion (CIV) for 72 hours or 120 hours every
other week using a standard dose escalation scheme; however the study
was subsequently amended, and after 2 cycles of CIV rigosertib (each
cycle being 2 weeks) patients were switched over to an oral regimen
consisting of 560mg of drug administered twice a day continuously for 20
weeks. The objectives of the Phase I arm were to define maximum
tolerated dose (MTD), dose limiting toxicities (DLT), and to identify
anti-leukemia activity; the Phase II arm characterized time to response
or progression, duration of response, and 6-month survival as well as
signs of clinical activity including disease stabilization and defined
hematological responses.

Mark Roschewski, M.D., and colleagues from the National Institutes of
Health in Bethesda, MD presented a poster entitled “Phase I study of ON
01910.Na (Rigosertib), a multikinase PI3K inhibitor in
relapsed/refractory B-cell malignancies.” This study enrolled patients
with relapsed/refractory chronic lymphocytic leukemia (CLL), mantle cell
lymphoma (MCL), multiple myeloma (MM), and hairy cell leukemia (HCL).
The primary endpoint of the study was safety and tolerability. All
patients were evaluated for toxicity, and 10 patients completed 4 cycles
of therapy and were evaluable for secondary anti-tumor endpoints.
Rigosertib was found to be well tolerated as a single agent with no dose
limiting toxicities.

Since single agent anti-tumor activity was not observed at the dose
levels tested, further development in lymphoid malignancies will explore
alternative single agent dosing schedules and/or combination therapy.

“The findings reported in these three presentations provide further
evidence of the safety, tolerability, and potential for broad utility of
rigosertib in a variety of hematological malignancies,” commented Ramesh
Kumar, President and CEO of Onconova. “These data will inform future
clinical studies of rigosertib and provide additional support for
ongoing advanced clinical studies in MDS. We look forward to reporting
data from the pivotal Phase III trial of rigosertib in high-risk MDS
patients in the second half of 2013.”

Rigosertib (ON 01910.Na) is a small molecule multikinase inhibitor that
targets the PI3- kinases and the PLK mitotic pathways, critical pathways
to the growth and survival of cancer cells. Phase I-III studies with
rigosertib have been conducted at leading institutions in the U.S. and
abroad in more than 800 patients with solid tumors and hematological
cancers, including myelodysplastic syndrome (MDS) and acute myeloid
leukemia (AML). A multi-site Phase III trial (ONTIME) in MDS patients is
being conducted under a Special Protocol Assessment (SPA) from the U.S.
Food and Drug Administration (FDA) and is being supported by an award
from the Therapeutics Acceleration Program of The Leukemia and Lymphoma
Society. Both the FDA and European Medicines Agency have granted Orphan
Drug Designation for the use of rigosertib in MDS. The rigosertib
clinical program in solid tumors is also advancing in a Phase III
adaptive design trial (ONTRAC) for pancreatic cancer. ONTRAC is a Phase
III, multicenter, randomized, controlled study (with an interim analysis
for futility) that compares the efficacy and safety of gemcitabine alone
vs. rigosertib combined with gemcitabine in patients with previously
untreated metastatic pancreatic cancer.

About Onconova Therapeutics, Inc.

Onconova Therapeutics, based in Newtown, PA and Pennington, NJ,
discovers and develops novel small molecule therapeutics directed
against targets involved in signal transduction, cell-cycle, and DNA
repair. The most advanced product, rigosertib (ON 01910.Na), is now in a
pivotal trial being conducted under a Special Protocol Assessment (SPA)
from the U.S. Food and Drug Administration (FDA) for myelodysplastic
syndrome (MDS), as well as in a Phase III trial for pancreatic cancer.
In addition to rigosertib, Onconova is developing two other clinical
stage products: Ex-RAD® (a radioprotectant) and ON 013105 (a
novel anti-cancer agent initially directed toward refractory lymphoma,
including mantle cell lymphoma). For additional information, please
visit http://www.onconova.com.